A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus:: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A
A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus:: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A
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DOI：
10.1093/emboj/cdf619
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发表时间：
2002-12-16
期刊：
影响因子：
11.4
通讯作者：
Narayana, SVL
中科院分区：
文献类型：
--
作者：
Deivanayagam, CCS;Wann, ER;Narayana, SVL
我们在此报告了金黄色葡萄球菌 MSCRAMM 的最小配体结合片段（聚集因子 A）的晶体结构。该纤维蛋白原结合片段包含两个类似的折叠结构域。观察到的折叠是免疫球蛋白基序的新变体，我们称之为 DE 变体或 DEv-IgG 折叠。该亚组包括胶原蛋白结合金黄色葡萄球菌 MSCRAMM CNA 的配体结合结构域，以及许多以前归类为果冻卷的其他结构。结构预测表明，迄今为止鉴定的四种纤维蛋白原结合金黄色葡萄球菌 MSCRAMM 也包含相同的 DEv-IgG 折叠。使用纤维蛋白原γ链的C端区域作为探针进行的系统对接搜索表明，在聚集因子的两个DEv-IgG结构域之间形成疏水口袋作为配体结合位点。聚集因子中残基 Tyr256、Pro336、Tyr338 和 Lys389 的诱变取代被认为与 γ 链的末端残基 (408)AGDV(411) 接触，导致蛋白质对纤维蛋白原没有亲和力或显着降低。
We report here the crystal structure of the minimal ligand-binding segment of the Staphylococcus aureus MSCRAMM, clumping factor A. This fibrinogen-binding segment contains two similarly folded domains. The fold observed is a new variant of the immunoglobulin motif that we have called DE-variant or the DEv-IgG fold. This subgroup includes the ligand-binding domain of the collagen-binding S.aureus MSCRAMM CNA, and many other structures previously classified as jelly rolls. Structure predictions suggest that the four fibrinogen-binding S.aureus MSCRAMMs identified so far would also contain the same DEv-IgG fold. A systematic docking search using the C-terminal region of the fibrinogen gamma-chain as a probe suggested that a hydrophobic pocket formed between the two DEv-IgG domains of the clumping factor as the ligand-binding site. Mutagenic substitution of residues Tyr256, Pro336, Tyr338 and Lys389 in the clumping factor, which are proposed to contact the terminal residues (408)AGDV(411) of the gamma-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.